Human Leukocyte Antigen (HLA) typing (determining specific HLA alleles which an individual expresses at each class I and/or class II loci) is a useful tool for basic and clinical immunology research. For instance, HLA typing has been used to identify immunogenetic risk factors for human diseases and more recently has been used to investigate how pathogens (such as HIV) evolve in response to HLA-restricted immune selective pressures. HLA typing may also be useful in connection with vaccine research—the identification and mapping of HLA-restricted T-cell epitopes in the proteomes of difference pathogens may be used to inform a selection of potential immunogens in a T-cell based vaccine design. Further, HLA typing may be used in connection with transplantation medicine, such as for hematopoietic stem cell transplants: in order to minimize risk of rejection, donors and unrelated recipients are desirably matched with respect to HLA alleles.
HLA typing has conventionally been performed using low-resolution antibody-based serological tests. In addition, HLA typing can be achieved using molecular (DNA-based) methods. Molecular methods for HLA typing include hybridization with sequence-specific oligonucleotide probes, PCR amplification with sequence-specific primers, and DNA sequence-based methods.
Due to a relative high (and ever-increasing) number of identified HLA alleles (and thus growing list of ambiguous combinations), unambiguous HLA typing is costly, laborious, and limited to laboratories specializing in this work. For the purposes of scientific research, HLA types are often not unambiguously determined—rather, they are determined up to some “resolution” (level of ambiguity). Additionally, because the number of HLA alleles is constantly increasing, sequence-based, SSOP and SSP based typing results, which depend on the list of known alleles, require constant re-interpretation in light of newly-discovered alleles. This re-interpretation can result in more ambiguity than originally thought, and it is often impossible to re-type historic samples that may have been typed using lower-resolution approaches.
The practical consequence of these issues is that there is a large incongruence between the high-resolution HLA typing required for scientific investigations and the HLA typing that is widely available.